The present invention relates to a mass spectrometer and a method of mass spectrometry.
Tandem mass spectrometry, or MS/MS, has become the preferred technology for many applications in which mass spectrometry plays a part. Tandem mass spectrometry allows selection and isolation of specific compounds of interest and their subsequent identification. The extra selectivity of MS/MS enables this technology to be used for quantification of target compounds even in the presence of complex matrices.
Tandem mass spectrometers are known which comprise a mass filter, a collision cell arranged downstream of the mass filter which fragments selected parent or precursor ions, and a mass analyser which mass analyses the fragment or daughter ions which emerge from the collision cell. Ions are fragmented in the collision cell by Collision Induced Decomposition (“CID”) wherein ions undergo multiple collisions with gas molecules in the partially enclosed collision cell.
In most tandem mass spectrometers the processes of selecting specific parent or precursor ions, fragmenting the selected parent or precursor ions and mass analysing the resulting fragment or daughter ions takes place sequentially in space. The mass filter may be used to select parent or precursor ions of a target compound. The parent or precursor ions are then passed to a collision cell which fragments those parent or precursor ions. The mass analyser is then used to mass analyse the resulting fragment or daughter ions.
One known tandem mass spectrometer is commonly referred to as a triple quadrupole mass spectrometer. Triple quadrupole mass spectrometers comprise a first quadrupole rod set mass filter or mass analyser followed by a collision cell. A second quadrupole rod set mass filter or mass analyser is arranged downstream of the collision cell followed by an ion detector. The name triple quadrupole is derived from the first such instrument wherein an RF quadrupole was used to guide ions through the collision cell.
The first quadrupole rod set mass filter is typically used to select parent or precursor ions having a specific mass to charge ratio. Therefore, in order to record a full mass spectrum, the first quadrupole rod set mass filter must be scanned across the full mass to charge ratio range in order to sequentially transmit ions having different mass to charge ratios. The duty cycle for this process is relatively low and as a consequence the sensitivity of a quadrupole rod set mass filter when used to record a full mass spectrum is relatively poor. On the other hand, the quadrupole mass filter will have 100% duty cycle when used to transmit ions having a specific mass to charge ratio.
A triple quadrupole mass spectrometer may be used for Selected Reaction Monitoring (“SRM”) experiments wherein parent or precursor ions having a specific mass to charge ratio are arranged to be transmitted by the first quadrupole rod set mass filter arranged upstream of the collision cell. The specific parent or precursor ions are then transmitted to the collision cell and are fragmented thereby forming fragment or daughter ions. The second mass filter is arranged so as to transmit fragment or daughter ions having a specific mass to charge ratio. This arrangement is very specific and exceptionally sensitive. Triple quadrupole mass spectrometers have found significant use in the drug discovery and development process where they are used both for Selected Reaction Monitoring experiments and also for Multiple Reaction Monitoring (“MRM”) experiments to quantify target compounds of biological significance.
A limitation of conventional triple quadrupole mass spectrometers becomes evident when a conventional mass spectrometer is attempted to be used in a Multiple Reaction Monitoring (MRM) mode to monitor many different transitions or reactions. For each additional reaction that is included in an experiment, there is a corresponding reduction in the sampling duty cycle for each reaction monitored. For confirmation or validation of certain quantification analyses it is desirable to monitor several reactions. Indeed, for some applications it is a regulatory requirement to monitor several reactions in order to confirm or validate the quantification analysis.
A common application in peptide and protein analysis for a triple quadrupole mass spectrometer makes use of a parent or precursor ion scanning mode of operation. In this mode of operation the second mass filter or mass analyser arranged downstream of the collision cell is set so as to transmit only a specific characteristic fragment or daughter ion. The first mass filter arranged upstream of the collision cell is scanned so as to sequentially transmit different parent or precursor ions to the collision cell for subsequent fragmentation. When a specific fragment or daughter ion is detected then the mass to charge ratio of the corresponding parent or precursor ions which were transmitted by the first mass filter upstream of the collision cell are recorded. This approach has proved particularly useful in the analysis of protein post-translational modifications such as phosphorylation and glycosylation. However, since it is necessary to scan the first quadrupole mass filter upstream of the collision cell then the sampling duty cycle can be quite low, commonly less than 1%, and consequently the sensitivity is also relatively low.
It is therefore desired to provide an improved mass spectrometer and method of mass spectrometry which does not suffer from some or all of the disadvantages of the prior art.